# Mechanisms that Govern and Promote Cardiovascular Regeneration

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $755,017

## Abstract

PROJECT SUMMARY
Cardiovascular disease is common and deadly. While lower organisms have a
tremendous capacity for regeneration, the adult mammalian heart is more limited in its
capacity for regeneration and remuscularization of the damaged tissue following an
insult such as a myocardial infarction. Recently, we defined an evolutionary conserved
Shh-Gli1-Mycn cascade in newt, mouse and human that promotes cardiomyocyte
proliferation in vitro and cardiac repair. These studies used pharmacological agents,
genetic mouse models, viral vectors, fate mapping techniques, molecular biological
technologies, and time lapse videomicroscopy. Importantly, the results of these studies
and these tools and reagents provide a platform for the proposed studies that will dissect
the mechanisms that govern cardiovascular proliferation. Therefore, our overall
hypothesis is that the Shh downstream effector, Mycn, regulates cardiomyocyte
and endothelial cellular proliferation. In these proposed studies, we will use a number
of novel genetic models that we have engineered, bioinformatics algorithms that we
developed and we take an innovative approach to dissect the role of Mycn as an
important factor that governs cardiovascular proliferation. To examine our hypotheses,
we will address the following specific aims: Specific Aim #1: To define the role of
Mycn in the endothelial and cardiomyocyte lineages; Specific Aim #2: To define
the impact of Mycn overexpression in cardiovascular lineages and Specific Aim
#3: To define the Mycn targets in the cardiomyocyte lineage. These aims will utilize
our recently engineered genetic mouse models, inducible viral vectors, modified mRNA-
GFP constructs, ATAC-seq, MNase-seq, ChIP-seq, and bioinformatics algorithms to
comprehensively define the role for Mycn as an essential factor that governs
cardiomyocyte and endothelial cell proliferation and will promote heart regeneration
following injury. Given the tremendous morbidity and mortality of cardiovascular disease
in our society, the potential impact of this proposal is tremendous.

## Key facts

- **NIH application ID:** 10210329
- **Project number:** 5R01HL148599-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** MARY G GARRY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $755,017
- **Award type:** 5
- **Project period:** 2019-07-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210329

## Citation

> US National Institutes of Health, RePORTER application 10210329, Mechanisms that Govern and Promote Cardiovascular Regeneration (5R01HL148599-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10210329. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*